Ziconotide: what the evidence shows

What the human research shows

The most unusual molecule on this site: a venom peptide, delivered by implanted pump into cerebrospinal fluid, for pain that nothing else touches. Graded B rather than A — the trial quoted here is a 111-patient study that the journal later flagged as a duplicate publication, and the therapeutic window is narrow enough that the boxed warning is the first thing to read.

Evidence profile0–5

Metabolic & weight—0.0
Cardiovascular—0.0
Muscle & growth—0.0
Healing & repairB2.3
Neuro & sleep—0.0
Immune & inflammation—0.0
Sexual & hormonal—0.0
Skin & appearance—0.0
Ageing & longevity—0.0

Each score is confidence × effect size, taken from the best-evidenced benefit in that domain: the grade (A–D) sets the confidence, the measured effect sets the size. Hover a domain to see the outcomes behind it. Adverse effects are excluded and listed separately below.

Outcome	Grade	Effect size	Human studies	Where the evidence comes from
Severe cancer or AIDS-related pain	BProbable	Moderate	1 phase 3 RCT (n=111)	A randomised placebo-controlled trial in 111 patients with severe pain despite intrathecal opioids found a mean 53.1% improvement in pain scores against 18.1% on placebo, sustained through the maintenance phase. The result is real and the record is messy: JAMA later published a notice of duplicate publication about this article and an accompanying editorial.1 2 3
Absence of tolerance and dependence	BProbable	Moderate	Phase 3 programme; label	Ziconotide does not act on opioid receptors, so there is no tolerance, no dose escalation of the kind opioids require, and no withdrawal syndrome. The trial's maintenance phase showed no loss of effect. This is the central clinical argument for a drug that is otherwise very hard to use.1 4
Severe psychiatric and neurological effectsadverse	AEstablished	Large	Label boxed warning; approval programme	The Prialt label's boxed warning states that severe psychiatric symptoms and neurological impairment may occur during treatment, and that the drug is contraindicated in patients with a pre-existing history of psychosis. Hallucinations, confusion, depression and in some cases suicidality have been reported, and monitoring for cognitive and psychiatric change is built into the label. The dose–harm relationship is the limiting factor in practice.4
Delivery burdenadverse	AEstablished	Moderate	Label	Ziconotide is given only by continuous intrathecal infusion through an implanted or external pump — a surgical commitment with the infection and device risks that accompany it, and the reason it is a last-line therapy rather than an alternative to oral analgesia.4

AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 29 October 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

Registered trials

ClinicalTrials.gov lists 7 interventional studies naming Ziconotide as an intervention — 5 completed, and none with results posted to the registry.

A registration is not a result. Anyone can register a study, and many never report — so this list shows what has been attempted, not what has been shown. The graded evidence above is the answer to whether something works.

Study	Phase	Status	Participants	Sponsor	Results
Intrathecal Bolus Doses of ZiconotideNCT01373983 · started Aug 2011	Phase 4	Completed	26	University Hospital, Linkoeping	None
Ziconotide as First-Line IDTNCT03321955 · started Nov 2016	Phase 4	Completed	13	Albany Medical College	None
Single Shot Intrathecal Ziconotide for Painful Neuropathy or MyelopathyNCT01992562 · started Jan 2014	Phase 4	Withdrawn	0	Aaron Boster	None
Ziconotide Effectiveness and Safety Trial in Patients With Chronic Severe PainNCT00076544 · started Feb 2004	Phase 3	Completed	300*	Elan Pharmaceuticals	None
Prialt (Ziconotide) In Severe Chronic PainNCT00047749 · started Aug 2002	Phase 3	Completed	220*	Elan Pharmaceuticals	None
A Multicenter Phase II/III, Placebo-Controlled Study of SNX-111 Administered Intrathecally to Cancer and AIDS Patients With Chronic PainNCT00002160 · started —	Phase 2	Completed	100*	Neurex	None
Safety and Activity Study of Intrathecally Administered Ziconotide for Neuropathic Pain in Patients With CancerNCT00996983 · started Sept 2009	Phase 2	Unknown	16*	National Cancer Institute, Naples	None

Participant counts marked * are the sponsor's estimate, not a final enrolment. Source: ClinicalTrials.gov, read directly from the registry and refreshed weekly.

What it is

ω-Conotoxin MVIIA is one of the peptide toxins the predatory cone snail Conus magus uses to paralyse fish. It is 25 amino acids held by three disulfide bonds, and ziconotide is its synthetic copy — the first marine-derived peptide drug and still one of very few. Because it does not cross the blood-brain barrier, it has to be delivered directly into cerebrospinal fluid.

Its terminal half-life in CSF is around four and a half hours. It is a genuinely non-opioid analgesic for severe pain, and the clinical literature on it is as much about managing the psychiatric effects as about the analgesia.

How it is thought to work

N-type (Cav2.2) voltage-gated calcium channels sit on the presynaptic terminals of primary nociceptive neurons in the dorsal horn. Blocking them stops the calcium influx that releases glutamate and substance P, so the pain signal is not relayed up the cord. The same channels exist elsewhere in the central nervous system, which is where the psychiatric and cognitive adverse effects come from — the mechanism and the boxed warning are the same pharmacology in different places.

What is still unknown

How it compares with intrathecal opioids in a modern head-to-head; the trials are twenty years old.
Whether any dosing strategy avoids the psychiatric effects while keeping the analgesia.
Which patients respond — no predictor has been established.

The molecule and how long it lasts

Identity

Formula: C102H172N36O32S7
Molecular weight: 2639.2 g/mol
CAS number: 107452-89-1
PubChem: CID 16135415
Sequence: CKGKGAKCSRLMYDCCTGSCRSGKC-NH2

Three disulfide bridges.

PubChem record, read 29 October 2026; the sequence was derived from that record's own structure and checked against the product label where one exists.

Pharmacokinetics

Route: Intrathecal infusion by implanted or external pump
Half-life: About 4.6 hours terminal half-life in cerebrospinal fluid
Licensed regimen (Prialt): A continuous intrathecal infusion started at a low rate and titrated slowly upward within the label's maximum, with psychiatric and neurological monitoring

From the approved product's prescribing information: Prialt prescribing information (DailyMed) The regimen is the label's own wording, reproduced as a regulatory fact.

Regulatory status

European Union

Approved, prescription-only

Prialt authorised centrally in 2005 for severe chronic pain in patients requiring intrathecal analgesia. Specialist hospital use.

United States

Approved, prescription-only

Prialt approved in 2004 for severe chronic pain in patients for whom intrathecal therapy is warranted and who are intolerant of or refractory to other treatment. Boxed warning; contraindicated with a pre-existing history of psychosis.

United Kingdom

Licensed, prescription-only

Prialt licensed by the MHRA for intrathecal use.

Australia

Registered, Schedule 4

Registered for intrathecal use.

Canada

Not marketed

No current Drug Identification Number for ziconotide.

Sport (WADA)

Not prohibited

Not named on the Prohibited List.

Questions people actually ask

Is ziconotide stronger than morphine?

It is not comparable — it works on a different target, and it is used when intrathecal opioids have failed. In its trial in severe cancer and AIDS pain, scores improved 53% against 18% on placebo in patients already receiving intrathecal opioids.

Why the psychiatric boxed warning?

The calcium channels it blocks in the spinal cord also exist throughout the brain. Hallucinations, confusion and depression can occur, the label contraindicates it in anyone with a history of psychosis, and psychiatric monitoring is part of its use.

Can ziconotide be injected or taken orally?

No. It does not cross the blood-brain barrier, so it has to be infused directly into cerebrospinal fluid through a pump. There is no systemic formulation and no self-administered route.

One page per claimed effect

BDoes Ziconotide help with severe cancer or AIDS-related pain?1 phase 3 RCT (n=111)
BDoes Ziconotide help with absence of tolerance and dependence?Phase 3 programme; label
AHow common is severe psychiatric and neurological effects with Ziconotide?Label boxed warning; approval programme
AHow common is delivery burden with Ziconotide?Label

References

1
Staats PS, Yearwood T, Charapata SG, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.JAMA, 2004;291:63–70111 randomised. See the duplicate-publication notice below before citing this trial's size or novelty.
2
Notice of duplicate publication.JAMA, 2004The journal's notice concerning the ziconotide trial above.
3
Duplicate publication, multiple problems (editorial).JAMA, 2004Editorial accompanying the notice.
4
Prialt (ziconotide) intrathecal infusion prescribing information.DailyMed, read 29 Oct 2026Boxed warning, contraindication in pre-existing psychosis, intrathecal route, CSF terminal half-life about 4.6 hours, and the 25-amino-acid structure with three disulfide bonds.
5
PubChem compound record: ziconotide.PubChem, read 29 Oct 2026Formula, molecular weight, CAS and the 25-residue sequence used on this page.

Change log

2026-10-29Initial publication. Grade B on the pivotal trial, held below A because of the duplicate-publication notice; the psychiatric boxed-warning row graded A.